Abstract 3769: Biomarkers of Inflammation and Computer Assisted Intravital Microscopy Predict Microvascular Complications of Type 1 Diabetes
Type I diabetes (T1DM) is associated with increased vascular complications and is a pro-inflammatory state. The monocyte-macrophage is a pivotal cell in atherogenesis. However, there are scanty data on monocyte function and inflammation in T1DM. T1DM also exhibits significant and unique microvascular complications which has been very poorly studied. Thus, in this study, the specific aims were 1) To examine biomarkers of inflammation in T1DM with and without microvascular complications compared to matched controls and 2) To determine the microcirculatory abnormalities in T1DM with and without microvascular complications using computer assisted intravital microscopy (CAIM). Also, we tested if biomarkers of inflammation and monocyte function correlated with the presence of microvascular abnormalities as assessed by urinary albumin excretion and intravital microscopy. Following informed consent, fasting blood, 24 hr urine and CAIM measurements were obtained from T1DM with and without microvascular complications (T1DM-MV and T1DM) and matched controls (C) (n=50/group). Biomarkers of inflammation measured included plasma CRP, nitroty-rosine, monocyte superoxide and cytokines. All 3 groups were well-matched for age, BMI and the T1DM groups were matched for level of glycemia (HbA1C) and duration of diabetes. CRP and nitrotyrosine levels were elevated in T1DM and T1DM-MV compared to C (p<0.01). Also, monocyte superoxide, IL-1,TNF,IL-6 were significantly increased in T1DM and T1DM-MV compared to C (p<0.01). Severity index assessed by CAIM, was significantly increased in T1DM and T1DM-MV compared to C (p<0.001). Among the 2 T1DM groups, there was a significant increase in serum CRP, serum nitrotyrosine, monocyte superoxide anion release and IL-1 release in T1DM-MV compared to T1DM (P<0.05). This increased inflammation was associated with significant increase in microalbumin:creatinine ratio and CAIM severity score (p<0.01). Thus, T1DM-MV have increased inflammation compared to T1DM and C and IL-1, nitrotyrosine and CAIM provides an effective biomarker of early inflammation and diabetic complications. These markers can be monitored following therapies targeted at improving inflammation and micorvascular complications of T1DM.